人脑星形细胞瘤进展过程中Rho／ROCK信号通路的可能作用

目的探讨不同病理学级别人脑星形细胞瘤中Rho／ROCK信号通路可能扮演的角色。方法应用免疫组化法检测60例不同病理级别人脑星形细胞瘤组织中RhoA、RhoB、ROCK-1及ROCK-2蛋白表达，评估Rho/ROCK信号通路中RhoA、RhoB、ROCK-1及ROCK-2蛋白表达与星形细胞瘤的病理分级及临床特征的关系。结果（1）RhoA蛋白在瘤旁脑组织表达的阳性率为0，在低级别和高级别星形细胞瘤中表达的阳性率分别为20％和80％，高表达率分别为10．0％和66．7％；高级别组的阳性率和高表达率均高于瘤旁脑组织和低级别组（P〈0．05）；RhoA表达的强弱在一定程度上反映了人脑星形细胞瘤的恶性程度；（2）RhoA蛋白表达在〉40岁组的阳性率和高表达率均显著高于〈40岁组，两者差别均有统计学意义（P〈0．05）；（3）RhoA在右大脑半球组的高表达率显著高于左大脑半球组，差别有统计学意义（P〈0．05）；（4）RhoA蛋白表达的阳性率和高表达率与性别及肿瘤长径无关（P〉0．05）；（5）RhoB、ROCK-1及ROCK-2蛋白均为阴性表达。结论Rho/ROCK信号通路在人脑星形细胞瘤中的作用可能与RhoA／ROCK1，2及RhoB／ROCK1，2通路关系不大；RhoA在了解星形细胞瘤的发生、进展和寻找治疗新靶点方面有一定参考价值。

Possible role of Rho/ROCK pathway in progression of human brain astrocytomas

Objective To explore the role of the Rho small GTP-binding protein （Rho） and its major downstream target, ROCK （Rho-associated serine/threonine protein kinase） , in progression of human brain astrocytomas. Methods We examined the expression of RhoA, RhoB, ROCK-1 and ROCK-2 by immmunohistochemical methods, and analyzed the correlation of Rho/Rock pathway related molecules expression with elinicopathological characteristics in the 60 patients with astrocytomas. Results （ 1 ） The positivity rate of RhoA protein expression was 0 in brain tissues around tumor,20% in low-grade astrocytomas and 80% in high-grade astrocytomas. The overexpression rate of RhoA protein was 10% in low-grade astrocytomas and 66.7% in high- grade astrocytomas. The positivity rate and the overexpression rate were significantly higher in the high-grade astrocytomas group than in the low-grade astrocytomas group or the brain tissues around tumor group （ P 〈 0.05 ）. The positivity rate and the overexpression rate of RhoA protein expression were correlated with malignant grade.（2） The positivity rate and the overexpression rate of RhoA protein expression were correlated with age. The positivity rate and overexpression rate of RhoA protein expression were significantly higher in the age 〉 40 group than in the age 〈 40 group （ P 〈 0. 05）. （3） The overexpression rate of RhoA protein expression were correlated with tumors＇ site （ P 〈 0.05 ）. The overexpression rate of RhoA protein expression was significantly higher in the right cerebral hemisphere group than in the left cerebral hemisphere group. （4） The positivity rate and the over- expression rate of RhoA protein expression were not correlated with sex and the maximal diameter of tumors （P 〉 0.05）. （5） RhoB,ROCK-1 and ROCK-2 protein expression were negative in any group. Conclusions The function of Rho/ROCK pathway in human brain astrocytomas maybe have nothing to do with RhoA/ROCK1, RhoA/ROCK2 ,RhoB/ROCK1 or RhoB/ROCK2 pathway. RhoA may serve as a parameter for evaluating the carcinogenesis and progression in astrocytomas and may be a possible molecular target for treatment of this disease.